Bax dimerizes via a symmetric BH3:groove interface during apoptosis

Grant Dewson, S Ma, Paul Frederick, C Hockings, I TAN Tan, T Kratina, Ruth M Kluck

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Abstract

During apoptotic cell death, Bax and Bak change conformation and homo-oligomerize to permeabilize mitochondria. We recently reported that Bak homodimerizes via an interaction between the BH3 domain and hydrophobic surface groove, that this BH3:groove interaction is symmetric, and that symmetric dimers can be linked via the alpha6-helices to form the high order oligomers thought responsible for pore formation. We now show that Bax also dimerizes via a BH3:groove interaction after apoptotic signaling in cells and in mitochondrial fractions. BH3:groove dimers of Bax were symmetric as dimers but not higher order oligomers could be linked by cysteine residues placed in both the BH3 and groove. The BH3:groove interaction was evident in the majority of mitochondrial Bax after apoptotic signaling, and correlated strongly with cytochrome c release, supporting its central role in Bax function. A second interface between the Bax alpha6-helices was implicated by cysteine linkage studies, and could link dimers to higher order oligomers. We also found that a population of Bax:Bak heterodimers generated during apoptosis formed via a BH3:groove interaction, further demonstrating that Bax and Bak oligomerize via similar mechanisms. These findings highlight the importance of BH3:groove interactions in apoptosis regulation by the Bcl-2 protein family.
Original languageEnglish
Pages (from-to)661 - 670
Number of pages10
JournalCell Death and Differentiation
Volume19
Issue number4
DOIs
Publication statusPublished - 2012

Cite this

Dewson, G., Ma, S., Frederick, P., Hockings, C., Tan, I. TAN., Kratina, T., & Kluck, R. M. (2012). Bax dimerizes via a symmetric BH3:groove interface during apoptosis. Cell Death and Differentiation, 19(4), 661 - 670. https://doi.org/10.1038/cdd.2011.138